RESUMO
Some 13-azaprostanoic acid derivatives were shown to have a high cytoprotective activity against the damaging effect of ethanol on the gastric mucosa in non-strain rats and affect ATP- and arachidonate-induced platelet aggregation in the whole blood of rabbits and rats in a different way. The gastroprotective activity that is common to natural and synthetic prostanoids is not closely related to the chemical structure of the compounds. On the contrary, the trends of these compounds to affect the induced platelet aggregation depend on the modification of both the cyclic moiety and both chains of a prostanoid molecule.
Assuntos
Mucosa Gástrica/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Ácidos Prostanoicos/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Etanol , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Ácidos Prostanoicos/uso terapêutico , Coelhos , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
In in vitro experiments on a model of arachidonate- and thrombin-induced platelet aggregation, analogues of PG endoperoxides displayed an antiaggregatory effect or stimulated spontaneous platelet aggregation in the whole blood of man and rabbits, but a slight antiaggregatory effect in the rabbit intact organism. The presence of the hydroxyl group instead of the routine alkyl omega-chain produced an antiaggregatory effect due to TxA2 receptor blockade.
Assuntos
Endoperóxidos Sintéticos de Prostaglandinas/farmacologia , Tromboxano A2/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Prostaglandinas H/farmacologia , Coelhos , Ratos , Ratos Wistar , Receptores de Tromboxanos/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
The effects of 11 new analogues of 7-aza- and 13-azaprostanoic acid on platelet aggregation of the rat were studied in vitro and ex vivo. The analogues of 13-azaprostanoic acid in vitro (10(-7)-10(-8) mol/l) were found to exhibit the antiaggregation activity in the blood. The compounds containing five-member cycle are more active antiaggregants. They decrease by 70-80% the degree of platelet aggregation stimulated by thrombin and ADP. The modification of omega-chain of these analogues (alkyl, phenyl) exerts no effect on the antiaggregation activity. The antiaggregation action of these compounds in ex vivo condition (5-10 micrograms/kg) does not preserve. 7-azaprostanoids possess the proaggregation activity in vitro.